Parkinson disease
Parkinson disease
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DOI：
10.1038/nrdp.2017.13
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发表时间：
2017-03-23
影响因子：
81.5
通讯作者：
Lang, Anthony E.
中科院分区：
文献类型：
--
作者：
Poewe, Werner;Seppi, Klaus;Lang, Anthony E.
帕金森病是第二常见的神经退行性疾病，影响 2-3% 的 65 岁以上人群。黑质神经元损失导致纹状体多巴胺缺乏，细胞内包含物含有α-突触核蛋白聚集体，是帕金森病的神经病理学标志。整个中枢和外周自主神经系统的多种其他细胞类型也参与其中，可能从疾病早期开始。尽管临床诊断依赖于运动迟缓和其他主要运动特征的存在，但帕金森病与许多非运动症状相关，这些症状会增加整体残疾。潜在的分子发病机制涉及多种途径和机制：α-突触核蛋白蛋白质稳态、线粒体功能、氧化应激、钙稳态、轴突运输和神经炎症。最近对诊断生物标志物的研究利用了神经影像学，其中包括 PET、单光子发射 CT (SPECT) 和新型 MRI 技术在内的多种模式已被证明有助于早期诊断和鉴别诊断。帕金森病的治疗以纹状体多巴胺的药物替代为基础，此外还采用非多巴胺能方法来解决运动和非运动症状，以及针对那些出现顽固性左旋多巴相关运动并发症的患者进行深部脑刺激。实验疗法试图通过基于基因和细胞的方法恢复纹状体多巴胺，最近，α-突触核蛋白的聚集和细胞运输已成为治疗靶点。当前最大的挑战之一是确定前驱疾病阶段的标志物，这将使新的疾病缓解疗法能够更早地开始。
Parkinson disease is the second-most common neurodegenerative disorder that affects 2-3% of the population >= 65 years of age. Neuronal loss in the substantia nigra, which causes striatal dopamine deficiency, and intracellular inclusions containing aggregates of a-synuclein are the neuropathological hallmarks of Parkinson disease. Multiple other cell types throughout the central and peripheral autonomic nervous system are also involved, probably from early disease onwards. Although clinical diagnosis relies on the presence of bradykinesia and other cardinal motor features, Parkinson disease is associated with many non-motor symptoms that add to overall disability. The underlying molecular pathogenesis involves multiple pathways and mechanisms: a-synuclein proteostasis, mitochondrial function, oxidative stress, calcium homeostasis, axonal transport and neuroinflammation. Recent research into diagnostic biomarkers has taken advantage of neuroimaging in which several modalities, including PET, single-photon emission CT (SPECT) and novel MRI techniques, have been shown to aid early and differential diagnosis. Treatment of Parkinson disease is anchored on pharmacological substitution of striatal dopamine, in addition to non-dopaminergic approaches to address both motor and non-motor symptoms and deep brain stimulation for those developing intractable l-DOPA-related motor complications. Experimental therapies have tried to restore striatal dopamine by gene-based and cell-based approaches, and most recently, aggregation and cellular transport of a-synuclein have become therapeutic targets. One of the greatest current challenges is to identify markers for prodromal disease stages, which would allow novel disease-modifying therapies to be started earlier.